ABSTRACT Support is requested for a Keystone Symposia conference entitled Uncovering Mechanisms from Immune- Based Therapy in Cancer and Autoimmunity, organized by Drs. Daniel J. Cua, E. John Wherry and Carla V. Rothlin. The conference will be held in Breckenridge, Colorado from February 18-22, 2019. Significant progress has been made in the field of immunology over the past two decades. Therapeutic agents such as anti-TNF, anti-CD20, anti-CTLA4, and more recently, anti-PD1 have benefited countless patients. This is a unique time for immunologists and clinical scientists to learn from the sheer number of clinical trials assessing immune targets for treatment of cancer and autoimmunity. Currently, there are more than 500 clinical studies testing combinations of checkpoint inhibitors with other pathway antagonists, which will begin to uncover the ?immune mechanisms? driving the disease process. This is highlighted by the observation that more than 10-20% of patients treated with anti-PD1 and/or CTLA4 later suffer from autoimmunity (e.g., anti- PD1 treatment is linked to Type 1 diabetes and anti-CTLA-4 treatment is linked to inflammatory bowel disease). Response rate to cancer treatment is greater in patients with autoimmune predisposition; therefore the autoimmune side effect is in part associated with patient genetics. The meeting topics will include discussions of combination immunotherapies, the genetics of patient response, and strategies to reprogram adaptive and innate immunity, which are key to harnessing the immune system to fight cancer and autoimmune diseases. The meeting will end with a special closing lecture on the future of immunotherapy.